Nitric oxide influences injury-induced microglial migration and accumulation in the leech CNS

Aileen Chen, Shanta M. Kumar, Christie L. Sahley, Kenneth J. Muller

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


Damage to the leech or mammalian CNS increases nitric oxide (NO) production and causes accumulation of phagocytic microglial cells at the injury site. The aim of this study was to determine whether NO plays a role in microglial migration and accumulation at lesions in which NO is generated by a rapidly appearing endothelial nitric oxide synthase (eNOS) in leeches. Immunohistochemistry and cytochemistry demonstrated active eNOS before and throughout the period of microglial accumulation at the lesion. Decreasing NO synthesis by application of the NOS inhibitor N(w)-nitro-L-arginine methyl ester (1 mM) significantly reduced microglial accumulation, whereas its inactive enantiomer N(w)-nitro-D-arginine methyl ester (1 mM) resulted in microglial accumulation similar to that in crushed controls. Increasing NO with the donor spermine NONOate (SPNO) (1 mM) also inhibited accumulation, but not in the presence of the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5- teramethylimidazolineoxyl-3-oxide (50 μM). The effect of SPNO was reversed by washout. SPNO application reduced average microglial migratory speeds and even reversibly arrested cell movement, as measured in living nerve cords. These results suggest that NO produced at a lesion may be a stop signal for microglia to accumulate there and that it can act on microglia early in their migration. Thus, NO may assume a larger role in nerve repair and recovery from injury by modulating accumulation of microglia, which appear to be important for axonal regeneration.

Original languageEnglish (US)
Pages (from-to)1036-1043
Number of pages8
JournalJournal of Neuroscience
Issue number3
StatePublished - Feb 1 2000


  • Cell migration
  • Endothelial nitric oxide synthase
  • Hirudo medicinalis
  • Microglia
  • Nerve regeneration
  • Nerve repair
  • Nitric oxide

ASJC Scopus subject areas

  • Neuroscience(all)


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